Over 60% of homosexual men with Kaposi's sarcoma (KS), opportunistic infections, and the acquired immunodeficiency syndrome (AIDS) have high serum levels of an endogenously produced acid-labile alpha interferon (IFN). The proportion of IFN-positive patients increases with the severity of clinical illness in several homosexual populations. Since a similar IFN is also found in many patients with classic autoimmune diseases, this unusual IFN may be related to the immune disorders in patients with AIDS. Furthermore, many of the clinical features of AIDS closely resemble common side effects of IFN therapy, and are also very similar to symptoms of chronic infection with Epstein-Barr virus (EBV). The experiments in this proposal are therefore designed to test the hypothesis that endogenous IFN and/or chronic infection with EBV contribute to the etiology of AIDS. The objectives are to determine the significance of circulating IFN in patients with AIDS or with prodromal illnesses and the relationship between this IFN and reactivated EBV infections. We will therefore do longitudinal studies on the presence of IFN in homosexual patients with prodromes of AIDS, determine the level of IFN-induced 2 feet - 5 feet oligoadenylate synthetase in mononuclear cells from these patients, and quantitate and characterize IFN in sera from heterosexual patients with AIDS. We will monitor the amount the type of IFN in homosexual patients with KS before, during and after therapy with "conventional" IFN and determine whether IFN isolated from patients with AIDS or standard human IFNs have antitumor effects on an established KS cell line. We will also determine if mononuclear cells from IFN-positive homosexual patients with AIDS have active EBV infections (by measuring EBV-specific antigens and spontaneous outgrowth of lymphoblastoid cell lines), and study whether reactivation of EBV by chemical inducers results in synthesis of IFN or if IFN treatment of EBV-transformed non-producer cells has any effect on expression of EBV antigens. The results of these studies may provide a simple method for identifying prodromal patients at risk for AIDS, clues to the etiology of AIDS, and the data needed to make rational decisions concerning IFN therapy for KS in patients with AIDS.